INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
artículos
Título:
Liver Fatty Acid-binding Protein Binds Monoacylglycerol in Vitro and in Mouse Liver Cytosol
Autor/es:
LAGAKOS WS; GUAN X; HO SY; RODRIGUEZ SAWICKI LUCIANA; CÓRSICO BETINA; MUROTA K; STARK RE; STORCH JUDITH
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY (ONLINE)
Editorial:
American Society for Biochemistry and Molecular Biology
Referencias:
Año: 2013 p. 19805 - 19815
ISSN:
1083-351X
Resumen:
Liver fatty acid-binding protein
(LFABP; FABP1) is expressed both in
liver and intestinal mucosa. Mice null
for LFABP were recently shown to have
altered metabolism of not only fatty
acids but also monoacylglycerol, the two
major products of dietary
triacylglycerol hydrolysis (Lagakos et
al., Am J Physiol. 2011). Nevertheless,
the binding and transport of MG by
LFABP is uncertain, with conflicting
reports in the literature as to whether
this single chain amphiphile is in fact
bound by LFABP. In the present
studies, gel filtration chromatography of
liver cytosol from LFABP-/- mice shows
the absence of the low molecular weight
peak of radiolabeled monoolein present
in the fractions that contain LFABP incytosol from wild type mice, indicating
that LFABP binds sn-2 MG in vivo.
Further, solution state NMR
spectroscopy demonstrates two
molecules of sn-2-monoolein bound in
the LFABP binding pocket, in positions
similar to those found for oleate
binding. Equilibrium binding affinities
are approximately two-fold lower for
MG compared to FA. Finally, kinetic
studies examining the transfer of a
fluorescent MG analogue show that the
rate of transfer of MG is 7-fold faster
from LFABP to phospholipid
membranes than from membranes to
membranes, and occurs by an aqueous
diffusion mechanism. These results
provide strong support for
monoacylglycerol as a physiological
ligand for LFABP, and further suggest
that LFABP functions in the efficient
intracellular transport of MG.